What are the fetal risks if a pregnant woman takes bupropion and topiramate (Topamax) during the first week of gestation?

Exposure to Bupropion and Topiramate in the First Week of Pregnancy

If a woman takes bupropion and topiramate during the first week of pregnancy, the primary concern is topiramate's established association with oral clefts (particularly cleft lip), while bupropion carries a small increased risk of specific cardiac defects; however, exposure during the very first week may carry lower risk than later first-trimester exposure since organogenesis has not yet begun.

Understanding the Timing of Exposure

• The first week of pregnancy (calculated from the last menstrual period) typically occurs before implantation and before organogenesis begins, which starts around week 3-4 of gestation 1, 2
• Critical periods for the specific malformations associated with these medications occur later in the first trimester, particularly during weeks 4-10 when facial structures and cardiac structures are forming 3, 4
• However, any first-trimester exposure warrants careful counseling and monitoring 1, 2

Topiramate-Specific Risks

Topiramate poses the more significant teratogenic concern of the two medications, with a well-established association with oral clefts:

• The risk of oral clefts with first-trimester topiramate exposure is approximately 5.1% compared to 2.1% with lamotrigine (risk ratio 2.2; 95% CI 1.2-4.0) 3
• Specifically, topiramate is associated with cleft lip, with 1.4% of exposed infants developing this malformation 4
• The overall risk of major congenital malformations with topiramate is 4.2-5.1% 3, 4
• The FDA requires a Risk Evaluation and Mitigation Strategy specifically warning about orofacial clefts with first-trimester topiramate exposure 5

Additional Topiramate-Associated Malformations

• Possible increased risk of conotruncal heart defects, ventricular septal defects, atrial septal defects, hypospadias, and coarctation of the aorta 6
• Patent ductus arteriosus and obstructive genitourinary defects have also been identified as potential signals 6

Bupropion-Specific Risks

Bupropion carries a lower overall teratogenic risk but has been associated with specific cardiac defects:

• Bupropion does not appear to increase the overall risk of major congenital malformations significantly 5, 1
• A small absolute increase in two specific cardiovascular malformations has been reported: left ventricular outflow tract obstruction heart defects and ventricular septal defects (adjusted odds ratio 2.9; 95% CI 1.5-5.5) 5, 1
• Possible increased risk for diaphragmatic hernia (adjusted odds ratio 2.77; 95% CI 1.34-5.71), though the absolute risk is extremely small given the rarity of this condition (population prevalence 0.012%-0.031%) 5, 1
• Possible increased risk for spontaneous abortion 5, 1

Important Caveat About Bupropion Data

• Confounding by indication cannot be ruled out in bupropion studies, as the underlying maternal depression or smoking may contribute to observed risks 5, 1
• The absolute risk of cardiovascular defects, even if increased, remains relatively low 1, 2

Clinical Management Algorithm

Immediate Steps (Upon Discovery of Pregnancy)

1. Do not abruptly discontinue either medication without psychiatric/neurologic consultation, as untreated maternal conditions carry their own risks 1

2. Discontinue topiramate immediately if it was being used for weight management or migraine prophylaxis (non-essential indications), as all weight management medications are contraindicated in pregnancy 2

3. For topiramate used for epilepsy, consult neurology urgently to discuss switching to a lower-risk antiepileptic drug such as lamotrigine or levetiracetam, which have malformation risks of 2.0-2.4% 3, 4

4. For bupropion, engage in a risk-benefit discussion about continuing versus discontinuing, considering the severity of the underlying condition (depression, ADHD, or smoking cessation) 1, 2

Prenatal Monitoring Protocol

• Fetal anatomic ultrasound at 18-20 weeks with specific attention to:

  • Oral structures (cleft lip/palate screening for topiramate exposure) 3, 4
  • Cardiac structures (ventricular septal defects, left ventricular outflow tract, conotruncal defects) 5, 1, 6
  • Diaphragm (for bupropion exposure) 5, 1

• Consider fetal echocardiography at 20-22 weeks given the cardiac risks from both medications 5, 1, 6

• Serial fetal growth assessments throughout pregnancy 1

• Maternal blood pressure monitoring regularly 1

• Ensure appropriate maternal weight gain according to gestational guidelines 1

Counseling Points

• The very early timing of exposure (first week) may be somewhat reassuring, as this precedes the critical period of organogenesis, but does not eliminate risk entirely 1, 2

• The combination of both medications has not been specifically studied, so risks may be additive 5

• Even with the increased relative risks, the absolute risk of malformations remains in the single-digit percentage range for most defects 3, 4

Common Pitfalls to Avoid

• Do not assume "all-or-nothing" protection from the early timing; while the first week is before major organogenesis, continued exposure into weeks 3-10 would occur during critical developmental windows 3, 4

• Do not overlook the indication for topiramate—if used for epilepsy, abrupt discontinuation poses seizure risks that may outweigh teratogenic concerns; if used for weight loss or migraine, discontinuation is clearly indicated 5, 2

• Do not fail to document the risk-benefit discussion and shared decision-making process, particularly regarding continuation or discontinuation of bupropion 1, 2